The tumor-forming type of multiple myeloma. I. Biological behavior.

A total of 45 cases of multiple myeloma has been followed up clinically during the period from 7 to 80 months. Out of these, six patients (13.3%) were diagnosed to be the tumor-forming type; they developed discrete tumor formation at the disease onset or during clinical observation. Biological behavior of these cases is briefly outlined. Histologically, five cases presented with well or moderately well differentiated plasma cells according to the grading made by Pasmantier and Azar. The remaining one case was poorly differentiated in cell maturity, and with electron and immunofluorescence microscopies, proved to be of plasmacytic nature.</p

Prognostic factors in multiple myeloma treated with prednisolone and sequential melphalan and ifosfamide: MIP combination chemotherapy

Response rates and survival times were studied in 47 patients who had multiple myeloma and who were being treated with Prednisolone and sequential Melphalan and Ifosfamide (MIP therapy). The clinical response was determined by objective parameters such as the reduction of M-protein level, tumor volume and healing of bone destruction. Twenty-eight of the patients (59.6%) responded to the MIP therapy. The 50% survival time as followed from the initiation of treatment to death was 19 months. Of the prognostic factors, the age (greater than or equal to 70 years), clinical stage III of Durie and Salmon, hypercalcemia, extensive bone lesions, and the patho-morphological type IV of Brucher were associated with a decreased life-span. Therefore, MIP therapy was more effective in poor risk (high tumor mass group) than in good risk (low or intermediate tumor mass group) patients, but the survival of patients on MIP therapy was shorter in the poor risk group than in the good risk one. In addition, the group which responded rapidly (i.e. within 2-5 weeks) had longer remission and longer survival than the group which improved slowly (i.e. after 6-16 weeks).</p

Influences of Anti-leukemic Agents on the Hematopoietic Functions of Bone Marrow 3. Influences of Various Anti-leukemic Agents on Thrombopoietic Function of Normal Human and Guinea Pig Bone Marrow

In order to compare the influences of various anti-leukemic agents on the bone marrow thrombopoiesis, the clinical tissue culture of bone marrow from normal guinea pigs and healthy persons was conducted. Various anti-leukemic agents were added to the culture media at the maximum concentration where they would not inhibit the bone marrow growth in culture, and observations were carried out to see the influences of these agents on the function of megakaryocytes of bone marrow. As the results, the author arrived at the follwing conclusions. 1. Urethane. Nitromin. Demecolcin, Actinomycin C and Mitomycin C inhibit the thrombopoietic function of bone marrow to a high degree. 2. Thio-TEPA, 8-Azaguanine, Carzinophilin, and Chromomycin demonstrate a moderate inhibitory action on the thrombopoietic function of bone marrow. 3. 6-MP slightly inhibits the thrombopoietic function of bone marrow. 4. Myleran, and the combined use of 6-MP and Prednisolone show no inhibitory effect on the thrombopoietic function of bone marrow. 5. On the other hand, Prednisolone alone rather augments the bone marrow thrombopoietic function

Influences of Anti-leukemic Agents on Hematopoietic Functions of Bone Marrow 1. A Study on the Roller Culture Method of Bone-Marrow Cell Suspension

For the purpose of a comparative study on the influences of various anti-leukemic agents on the erythropoietic function of bone marrow, a roller culture method was performed to culture the cell suspensions of human and rabbit bone marrow. In the course of the incubation, the author observed the changes in the erythrocyte counts, number of nucleated cells, hemoglobin content, percentage of orthochromic erythroblasts, and increment index of orthochromic erythroblasts. As the results, it has been recognized that in this culture method bone marrow erythroblasts mature and differentiate in the same fashion as in in vivo. Therefore, it is assumed that, when human or rabbit bone marrow is cultured by this method in the media containing chemical substances or sera, it is possible to observe their direct influences on the erythropoietic functions of bone marrow

Studies on the Cell-free Transmission of X-ray and 20-Methylcholanthrene-induced RF Mouse Leukemia

Incidence of leukemia in RF mice exposed to a single whole body irradiation of 350 r X-rays was 77.4%, 41 out of 53 animals. Of them, 20 developed the thymic and other 20 the non-thymic lymphocytic leukemia, while only one developed myelogenous leukemia. Incidence of leukemia by 20-methylcholanthrene painting was 88%, 22 out of 25 animals. Of them, 12 developed lymphocytic leukemia and other 10 myelogenous leukemia. Experiments of inoculating cell-free filtrate prepared from these X-ray and 20-methylcholanthrene-induced leukemic RF mice revealed the following facts. 1) Cell-free filtrates from the leukemic mice which were induced by a single whole body X-irradiation were inoculated to the newborn mice of the same strain less than 16 hours old. Two (16.7%) of the twelve incculated animals developed leukemia 357 th and 374 th days, respectively, after the inoculation. Inoculation of the cell-free filtrates from normal mice to the newborn mice of the same strain did not produce leukemia. 2) Attempts to inoculate cell-free filtrate from 20-methylcholanthrene-indeced leukemic RF mice to newborn mice of the same strain were successful. 3) Cell-free filtrate from myelogenous leukemic mouse caused lymphocytic leukemia in one of three inoculated mice. This is suggestive of the possibility of transformation of the type of leukemia during cell-free transmission. 4) Intracerebral inoculation of cell-free filtrate from the brain of a mouse with lymphocytic leukemia also produced lymphocytic leukemia in one of two inoculated mice. 5) Inoculation of cell-free filtrate from the leukemic mice developed mammary carcinoma in one of three inoculated female mice. 6) Serial cell-free passage in two generations of 20-methylcholanthrene-induced leukemic mouse was possible. One of two inoculated mice developed leukemia in the first transmission and one of eight inoculated mice in the second transmission. 7) Only two cases of spontaneous lymphocytic leukemia were observed in RF mice during the past four years and the cell-free transmission of one leukemic mouse was also successful. 8) Virus-like particles were demonstrated by electron microscope in the lymph nodes of 20-methylcholanthrene-induced leukemic mouse. These facts suggest that the X-ray and chemical carcinogens may act to induce leukemia or mammary carcinoma by the "activation" of a latent virus naturally resident in the RF mouse

Studies on the Treatment of Malignant Tumors With Fibroblasts Inhibiting Agents Basic and Clinical Studies of Chloroquine Derivatives. (1)

Followings are the results derived from the treatment of animal and human cancers with a fibroblasts inhibiting agent such as chloroquine, based on the unique idea of ours. 1). In implanted tumors of animals, the effect was noted in Bashford cancer and Brown-Pearce cancer relatively rich in connective tissue in terms of life prolongation, an inhibition of tumor growth and of decrease of liver catalase activity, an improvement of iron metabolism, an enlargement of necrotic area in histology, an inhibition of connective tissue conponents, and a decrease of acid mucopolysaccharides. A tendency for a decrease of amount and cell numbers of ascites was almost the only effect noted in Ehrlich cancer, Yoshida sarcoma, and MH 134 poor in connective tissue. 2). 75 cases of humau cancer were treated with this agent and among these 75 the effect was evaluated in 40 cases with definite histological diagnosis in respects with subjective and objective improvement. It was effective in 28 cases, resulted failure in 11 cases, and gave an obscure result in 1 case. Cases which were treated for more than 2m onths never resulted in therapeutic failure, indicating that the agent was somehow effective for all cases but those in the last stadium. In respect with organs involved, the effect was most prominent in lung cancer and urinary bladder cancer, somewhat less in gastric cancer, and often seen in carcinomatous peritonitis and many other advanced cancers. This effect was noted in a comparatively short period in terms of subjective improvement, regression in size of tumors in a number of cases, a decrease of serum lactic acid dehydrogenase, and improvement of general condition, a tendency for necrosis of tumor and an inhibition of interstitium. 3). The above results indicate that the agent is more effective for tumors rich in connective tissue and that it's secondary effect on tumors through the inhibition of interstitial connective tissue is considered as the operative mechanism of chloroquine against malignant tumors, but it's anti-inflammatory effect and generalized influence on hosts are to be taken into consideration. The agent is indicated in inoperable cases, postoperative relapse, or prior and following an operation. A search for stronger fibroblasts inhibiting agents and an evaluation of combined therapy with so called anti-cancer agents are being made and that with mitomycin C is giving a fairly promising result

Studies on the Treatment of Malignant Tumors With Fibroblasts Inhibiting Agents Basic and Clinical Studies of Chloroquine Derivatives. (1)

Followings are the results derived from the treatment of animal and human cancers with a fibroblasts inhibiting agent such as chloroquine, based on the unique idea of ours. 1). In implanted tumors of animals, the effect was noted in Bashford cancer and Brown-Pearce cancer relatively rich in connective tissue in terms of life prolongation, an inhibition of tumor growth and of decrease of liver catalase activity, an improvement of iron metabolism, an enlargement of necrotic area in histology, an inhibition of connective tissue conponents, and a decrease of acid mucopolysaccharides. A tendency for a decrease of amount and cell numbers of ascites was almost the only effect noted in Ehrlich cancer, Yoshida sarcoma, and MH 134 poor in connective tissue. 2). 75 cases of humau cancer were treated with this agent and among these 75 the effect was evaluated in 40 cases with definite histological diagnosis in respects with subjective and objective improvement. It was effective in 28 cases, resulted failure in 11 cases, and gave an obscure result in 1 case. Cases which were treated for more than 2m onths never resulted in therapeutic failure, indicating that the agent was somehow effective for all cases but those in the last stadium. In respect with organs involved, the effect was most prominent in lung cancer and urinary bladder cancer, somewhat less in gastric cancer, and often seen in carcinomatous peritonitis and many other advanced cancers. This effect was noted in a comparatively short period in terms of subjective improvement, regression in size of tumors in a number of cases, a decrease of serum lactic acid dehydrogenase, and improvement of general condition, a tendency for necrosis of tumor and an inhibition of interstitium. 3). The above results indicate that the agent is more effective for tumors rich in connective tissue and that it's secondary effect on tumors through the inhibition of interstitial connective tissue is considered as the operative mechanism of chloroquine against malignant tumors, but it's anti-inflammatory effect and generalized influence on hosts are to be taken into consideration. The agent is indicated in inoperable cases, postoperative relapse, or prior and following an operation. A search for stronger fibroblasts inhibiting agents and an evaluation of combined therapy with so called anti-cancer agents are being made and that with mitomycin C is giving a fairly promising result

Morphology and Classification of Oncogenic Viruses

Morphologic characteristics of most of known oncogenic viruses, some of which were investigated by us, were described in relation to their oncogenicity and their localizations in tumor tissues. Oncogenic viruses were classified into six groups: type A, B, C, D, E and F. Viruses pertaining to type A were presumably not mature virus particles. Some of them could, however, be immature form or incomplete form of oncogenic virus particles. Viruses belonging to type B, C, D, E, and F were represented by mammary tumor virus of mice, leukemia viruses of mice and chickens, polyoma virus, Shope fibroma virus and Lucke renal adenocarcinoma virus, respectively. They were different in size and shape, and in the mode of development. It was presumed that type B and C viruses were members of the Myxovisus group and type D viruses belonged to Adenovirus and the Papova virus group. It was also believed that type E and F viruses had in general the feature of the Pox virus group and Herpes virus group, respectively